Circadian rhythms of nocturnal hormones in rheumatoid arthritis: translation from bench to bedside

Cutolo, Maurizio; Straub, Rainer H.; Buttgereit, Frank

doi:10.1136/ard.2008.088955

Cited by 67 publications

(48 citation statements)

References 33 publications

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“…Another important feature of RA would be a circadian manifestation of the disease such as morning stiffness, which is included in the diagnostic criteria of RA (2). Such circadian characteristic is also seen in the proinflammatory cytokines and disease-specific markers important in RA: IL-1b, IL-6, and TNF-a are all elevated in sera of rheumatoid patients reaching the peak levels in early morning (3)(4)(5)(6), and secretion of the IgA and IgM types of the rheumatoid factor also exhibits a rhythmic pattern with a peak at morning (7).…”

mentioning

confidence: 88%

Mammalian Clock Gene Cryptochrome Regulates Arthritis via Proinflammatory Cytokine TNF-α

Hashiramoto

Yamada

Tsumiyama

et al. 2009

The Journal of Immunology

158

143

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The mammalian clock genes, Period and Cryptochrome (Cry), regulate circadian rhythm. We show that circadian rhythmicity and rhythmic expression of Period in the nuclei of inflammatory synovial cells and spleen cells are disturbed in mouse models of experimental arthritis. Expressions of other clock genes, Bmal1 and Dbp, are also disturbed in spleen cells by arthritis induction. Deletion of Cry1 and Cry2 results in an increase in the number of activated CD3+ CD69+ T cells and a higher production of TNF-α from spleen cells. When arthritis is induced, Cry1−/−Cry2−/− mice develop maximal exacerbation of joint swelling, and upregulation of essential mediators of arthritis, including TNF-α, IL-1β and IL-6, and matrix metalloproteinase-3. Wee-1 kinase is solely upregulated in Cry1−/−Cry2−/− mice, in line with upregulation of c-Fos and Wee-1 kinase in human rheumatoid arthritis. The treatment with anti–TNF-α Ab significantly reduced the severity and halted the progression of the arthritis of Cry1−/−Cry2−/− mice and vice versa, ectopic expression of Cry1 in the mouse embryonic fibroblast from Cry1−/−Cry2−/− mice significantly reduced the trans activation of TNF-α gene. Thus, the biological clock and arthritis influence each other, and this interplay can influence human health and disease.

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mentioning

confidence: 88%

Mammalian Clock Gene Cryptochrome Regulates Arthritis via Proinflammatory Cytokine TNF-α

Hashiramoto

Yamada

Tsumiyama

et al. 2009

The Journal of Immunology

158

143

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“…Highly elevated concentrations of proinflammatory cytokines are observed in patients with active RA in the early hours of the day [3]. Their release pattern follow a 24-h circadian cycle, which implicates that serum concentrations may be under the control of neuroendocrine center in the hypothalamus [1].…”

Section: Introductionmentioning

confidence: 94%

“…It has been known for many decades that disease symptoms in rheumatoid arthritis (RA) follow obvious circadian rhythms, with an increased activity in the early morning hours, abatement during the day, and a smaller new increase in the early evening [1]. Studies have reported a temporal relationship between stimulated levels of proinflammatory cytokines and symptoms of RA, such as morning stiffness [1,2].…”

Section: Introductionmentioning

confidence: 99%

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Melatonin attenuates clock gene Cryptochrome1, which may aggravates mouse anti-type II collagen antibody-induced arthritis

et al. 2010

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Very recently, the circadian rhythm was proved to play an important role in the pathogenesis of arthritis. The role of melatonin in the development and progress of rheumatoid arthritis has been implicated for decades. This study was aimed to investigate the effect of melatonin on the expression of circadian clock genes in mouse anti-type II collagen antibody-induced arthritis (CIA). Mice were divided into 3 groups: control, CIA, and CIA + melatonin treatment (MLT). Both mRNA and protein levels of circadian clock gene Cryptochrome1 (Cry1) were markedly decreased in CIA + MEL group compared with those in control and CIA groups. MLT increased paw thickness. Histologic and X-ray assessment also revealed increased infiltration of inflammatory cells, synovial hyperplasia, and the destruction of articular cartilage and bone by MLT. The concentrations of anti-type II collagen antibody in CIA + MEL group mice were significantly higher than those in control and CIA groups (P < 0.05). Serum concentrations of TNF-α (P < 0.005) and IL-6 (P < 0.05) in CIA + MLT group were also increased. Taken together, these results implicate that clock gene Cry1 may be involved in the aggravation of MLT-mediated arthritis in mice anti-type II collagen antibody-induced arthritis.

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“…With recent insights into the role of endogenous and exogenous GCs [21], and a better understanding of the involvement of neuroendocrine pathways in the function of the HPA axis and their interplay with the immune system in RA [22,23,24,25,26], new treatment options arose. The basis was found by Arvidson et al [27] when proposing that key symptoms such as morning stiffness in RA were likely to be attributable to circadian rhythms of plasma concentrations of IL-6 (which peaked in the morning and abated during the day).…”

Section: Circadian Rhythms and Hpa Axis Deficiency In Patients With Ramentioning

confidence: 99%

Hypothalamic-Pituitary-Adrenal Axis Function in Patients with Rheumatoid Arthritis Treated with Different Glucocorticoid Approaches

Alten¹,

Wiebe²

2014

Neuroimmunomodulation

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Glucocorticoids (GCs) continue to be an important treatment option in rheumatoid arthritis (RA) - despite their multitude of side effects. Amongst those, suppression of the hypothalamic-pituitary-adrenal (HPA) axis plays a dominant role. In clinical practice, low-dose GC therapy of 5 mg or less per day seems to be safest in eschewing these undesirable effects and assuring function of the HPA axis. Further research has shown that, apart from dosage, the degree of HPA axis suppression by exogenous GCs is not only dependent on the duration of therapy, but that it also underlies a significant diurnal variation. The recent development of a novel modified-release (MR) prednisone formula reflects an attempt at targeting these circadian neuroendocrine pathways of the HPA axis' function and their interplay with the immune system in RA. Data from a subset of 28 patients included in the CAPRA-1 study indicated that chronotherapy with MR prednisone has no adverse effect on HPA function. Whether adapting GC therapy to a pathophysiological circadian pattern might even be beneficial will have to be further investigated.

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Circadian rhythms of nocturnal hormones in rheumatoid arthritis: translation from bench to bedside

Cited by 67 publications

References 33 publications

Mammalian Clock Gene Cryptochrome Regulates Arthritis via Proinflammatory Cytokine TNF-α

Mammalian Clock Gene Cryptochrome Regulates Arthritis via Proinflammatory Cytokine TNF-α

Melatonin attenuates clock gene Cryptochrome1, which may aggravates mouse anti-type II collagen antibody-induced arthritis

Hypothalamic-Pituitary-Adrenal Axis Function in Patients with Rheumatoid Arthritis Treated with Different Glucocorticoid Approaches

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